Obstructive and central sleep apnea combination therapy control

ABSTRACT

Apnea events may be detected based on a primary biomarker, e.g., respiration, in the one or more physiological signals. The apnea events may be characterized as one of an obstructive sleep apnea (OSA) event, a central sleep apnea (CSA) event, or a combination OSA/CSA event based on a secondary biomarker, e.g., a frequency spectrum or a morphology of the respirations in the one or more physiological signals. A first electrical stimulation may be provided to treat OSA in response to a first one or more of the apnea events being characterized as OSA events. A second electrical stimulation may be provided to treat CSA in response to a second one or more of apnea events being characterized as CSA events. A third electrical stimulation may be provided to treat combination OSA/CSA in response to a third one or more of the apnea events being characterized as combination OSA/CSA events.

This application claims the benefit of U.S. Provisional Application Ser.No. 62/993,178, filed Mar. 23, 2020, the entire content of which isincorporated herein by reference.

TECHNICAL FIELD

This disclosure relates to techniques for detection and treatment ofsleep apnea and, more particularly, electrical stimulation for treatmentof obstructive sleep apnea (OSA), central sleep apnea (CSA) and mixedapnea (i.e., both OSA & CSA).

BACKGROUND

Apnea is a relatively common form of disordered breathing characterizedby interruptions to a patient's breathing. Often, the interruptions tobreathing occur during sleep, at which time the disorder is called sleepapnea. Breathing cessation may occur numerous times during sleep, insome cases hundreds of times a night. Each cessation of breathing maylast for up to a minute or longer.

Sleep apnea has multiple classifications based on the source of thedysfunction. For example, CSA results from neurological dysfunction,while OSA results form a mechanical blockage of the airway. Themechanical blockage may be due, for example, to fatty neck tissuecompressing the trachea.

OSA, which encompasses apnea and hypopnea, is a serious disorder inwhich breathing is irregularly and repeatedly stopped and started duringsleep, resulting in disrupted sleep and reducing blood oxygen levels.OSA is caused by complete or partial collapse of the pharynx duringsleep. Muscles in a patient's throat intermittently relax therebyobstructing the upper airway while sleeping. Airflow into the upperairway may be obstructed by the tongue or soft pallet moving to the backof the throat and covering a smaller than normal airway. Loss of airflow also causes unusual inter-thoracic pressure as a person tries tobreathe with a blocked airway. Lack of adequate levels of oxygen duringsleep may contribute to abnormal heart rhythms, heart attack, heartfailure, high blood pressure, stroke, memory problems and increasedaccidents. Additionally, loss of sleep occurs when a person is awakenedduring an apneic episode. Implantable medical devices capable ofdelivering electrical stimulation pulses have been proposed for treatingOSA by electrically stimulating muscles around the upper airway that mayblock the airway during sleep and/or neurological structures innervatingthese muscles, such as the hypoglossal nerve.

Unlike OSA, CSA does not necessarily involve blockage of an airway.Instead, CSA involves failure of the brain to send appropriate signalsto initiate action of the muscles required for respiration. CSA occursduring sleep when an acute increase in ventilation results in a decreasein the level of carbon dioxide in a patient's bloodstream (i.e., thePaCO₂). When the PaCO₂ falls below a threshold level required tostimulate breathing, the “central” (as in Central Nervous System) driveto respiratory muscles and airflow ceases, initiating central apnea.This apnea persists until the patient's PaCO₂ level rises above thethreshold required to stimulate ventilation, upon which the cycle ofhyperpnea followed by apnea may repeat. This is referred to as “periodicbreathing”. Implantable medical devices capable of delivering electricalstimulation pulses have been proposed for treating CSA by electricallystimulating neurological targets that control respiration, such as thephrenic nerve.

In a general population of patients diagnosed with sleep apnea,approximately 90% will have OSA and approximately 10% will have CSA.Approximately 5% will have Mixed OSA+CSA (i.e., exhibit both OSA and CSAat different times).

SUMMARY

The techniques of this disclosure generally relate to an implantablemedical device (IMD) system and methods for delivering OSA, CSA, andcombination OSA/CSA therapy. Therapy delivery circuitry, e.g., of anIMD, may be configured to deliver a first electrical stimulation via afirst lead. The first lead may have a first plurality of electrodes. Thetherapy delivery circuitry may be configured to deliver secondelectrical stimulation via a second lead having a second plurality ofelectrodes. The IMD system may have processing circuitry configured tocontrol the therapy delivery circuitry to deliver the first electricalstimulation configured to treat OSA and control the therapy deliverycircuitry to deliver the second electrical stimulation configured totreat CSA. The first plurality of electrodes may be located along adistal portion of the first lead configured to be implanted withinmusculature of a tongue of a patient stimulating one or both hypoglossalnerves and/or motor points. The second plurality of electrodes may belocated along a distal portion of the second lead configured to beimplanted intravascularly proximate to a phrenic nerve within thepatient.

In an example technique, a method includes receiving one or morephysiological signals. Each of the one or more physiological signals mayinclude respirations of a patient. Apnea events may be detected based ona primary biomarker in the one or more physiological signals. Each ofthe apnea events may be characterized as one of a normal event, an OSAevent, a CSA event, or a combination OSA/CSA event based on a secondarybiomarker in the one or more physiological signals. A first electricalstimulation provided may be configured to treat OSA in response to afirst one or more of the apnea events being characterized as OSA events.A second electrical stimulation may be provided configured to treat CSAin response to a second one or more of apnea events being characterizedas CSA events. A third electrical stimulation may be provided configuredto treat combination OSA/CSA in response to a third one or more of theapnea events being characterized as combination OSA/CSA events.

In an example technique, a system may have therapy delivery circuitryconfigured to be coupled to a first lead comprising a first plurality ofelectrodes and a second lead comprising a second plurality ofelectrodes. The therapy delivery circuitry may deliver a firstelectrical stimulation via the first lead. The first electricalstimulation may be configured to treat OSA. A second electricalstimulation delivered via the second lead may be configured to treatCSA. Sensing circuitry may be configured to sense one or morephysiological signals. Each of the one or more physiological signals mayinclude respirations of a patient. Processing circuitry may beconfigured to detect apnea events based on timing of the respirations,determine at least one of a frequency spectrum or a morphology of therespirations based on the detection of the apnea events and characterizethe apnea events as one of normal, OSA, CSA, or combination OSA/CSAevents based on the at least one of the frequency spectrum or themorphology of the respirations. Based on the characterization of theapneas, the processing circuitry may control the therapy deliverycircuitry to deliver one of no electrical stimulation, the firstelectrical stimulation, the second electrical stimulation, or both thefirst and second electrical stimulation in combination.

In an example technique, an implantable medical device may be configuredto be coupled to a first lead comprising a first plurality of electrodesand a second lead comprising a second plurality of electrodes. Theimplantable medical device may have therapy delivery circuitryconfigured to deliver a first electrical stimulation via the first lead.The first electrical stimulation configured to treat OSA and a secondelectrical stimulation via the second lead configured to treat CSA.Sensing circuitry may be configured to sense one or more physiologicalsignals. Processing circuitry may be configured to detect respirationsin the one or more physiological signals, detect an apnea event based onthe respirations detected in the one or more sensed physiologicalsignals and characterize the apnea as one of obstructive sleep apnea(OSA), central sleep apnea (CSA), or mixed sleep apnea (OSA/CSA) basedon at least one of a frequency spectrum or a morphology of therespirations. Based on the characterization of the apneas, theprocessing circuitry may control the therapy delivery circuitry todeliver one of the first electrical stimulation, the second electricalstimulation, or both the first and second electrical stimulation incombination.

The details of one or more examples of the disclosure are set forth inthe accompanying drawings and the description below. Other features,objects, and advantages of the techniques described in this disclosurewill be apparent from the description and drawings, and from the claims.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a conceptual diagram of an IMD system for delivering OSA, CSAand/or mixed OSA/CSA therapy according to one or more examples.

FIG. 2 is a conceptual diagram of an example lead for delivering OSAtherapy according to one or more examples.

FIG. 3 is a conceptual diagram illustrating example locations of motorpoints where stimulation for OSA therapy may be delivered.

FIGS. 4A and 4B are conceptual diagrams of example electrical leads usedfor stimulation of the phrenic nerve in delivering CSA therapy accordingto one or more examples.

FIG. 5 is block diagram illustrating example configurations ofimplantable medical devices (IMDs) which may be utilized in the systemof FIG. 1.

FIG. 6 is a block diagram illustrating an example configuration of anexternal device according to one or more examples.

FIG. 7 is a flow diagram of an example method for detecting and treatingOSA, CSA, and combination OSA/CSA according to one or more examples.

FIGS. 8A, 8B, 8C and 8D are graphical diagrams of sleep spectrogramsaccording to one or more examples.

DETAILED DESCRIPTION

A medical device system for delivering electrical stimulation to theprotrusor muscles of the tongue for the treatment of OSA, to the phrenicnerve for the treatment of CSA, and to both the protrusor muscles andthe phrenic nerve for the treatment of combination OSA/CSA is describedherein.

In general, the disclosure is directed to techniques for detecting andmonitoring the respiratory function of a patient, e.g., based ondetection of abnormal breathing patterns. In some examples, abnormalbreathing patterns or other changes in patient status are detected basedon accelerometer signals, cardiac electrogram, electrocardiogram (ECG),or other cardiac electrical signals, and/or impedance signals. Examplesof this disclosure involve monitoring physiological signals, such asaccelerometer signals, subcutaneous ECG signals and/or bioimpedancesignals, using a subcutaneous IMD. In some examples, a subcutaneous IMDmay use single source physiologic signal, such as an accelerometersignal, a subcutaneous ECG signal, or a bioimpedance signal, or combinethem in any manner to improve detection sensitivity. In general, thephysiological signal may be able to provide diagnostic information aboutphysical parameters including respiratory rate, respiratory breathinganomalies and sleep apnea. For example, respiratory anomalies such asOSA, CSA or respiratory patterns associated with mixed OSA/CSA may bedetected with a subcutaneous sensor placed on the thorax which maydetect changes in respiratory rate or respiratory depth, cessation ofrespiration, and/or other respiratory characteristics associated withapnea. In some examples, respiratory parameters associated with “normal”or “healthy” respiration may also be identified.

FIG. 1 is a conceptual diagram of a medical system for delivering OSA,CSA and/or mixed OSA/CSA therapy. In system 10, IMD 16 and leads 20, 21are implanted in patient 14. In an example, it is possible to provideboth OSA and CSA therapy using a single IMD 16.

IMD 16 includes housing 15 enclosing circuitry of IMD 16. In someexamples, IMD 16 includes connector assembly 17, which is hermeticallysealed to housing 15 and includes one or more connector bores forreceiving medical electrical leads 20 and or 21 used for delivering CSAand OSA therapy, respectively. Although two leads 20 and 21 areillustrated in FIG. 1, there may be more than leads 20, 21 to which IMD16 is coupled. For example, an adaptor may be used to provide for two ormore leads extending from one connector bore (not shown) on connectorassembly 17.

Lead 21 has a proximal end 23 coupled to connector assembly 17 and adistal end 26. Distal end 26 is located at or near one or more motorpoints, one or more protrusor muscles or hypoglossal nerves 11, and/ormotor points 54A, 54B, 55A and 55B (FIG. 3), e.g., one or more locationswhere axons of the hypoglossal nerve 11 terminate at respective musclefibers of the protrusor muscles 42 and/or 46 (FIG. 2). Lead 20 also hasa proximal end 24, which is coupled within connector assembly 17, and adistal portion 25, which extends near phrenic nerve(s) 27 for deliveringCSA therapy. FIG. 1 illustrates lead 20 located at or near one of twophrenic nerves so electrodes, e.g., electrodes 130 of FIGS. 4A and 4B,could be used to provide therapeutic stimulation to one or both ofphrenic nerves 27. Using a subclavian approach, electrical lead 20 maybe placed in the left pericardiophrenic vein.

In some examples, system 10 may be an asynchronous system. In someexamples, system 10 is a synchronous system. Synchronous, for thepurposes of the present disclosure may relate to synchronizing orcoordinating therapy with a patient's breathing.

Additionally, processing circuitry of system 10 may control the deliveryof therapy, e.g., turn the stimulating therapy on and off, based onsensing feedback from sensing circuitry 56 (FIG. 5). The sensingfeedback may indicate whether the patient is experiencing apneas. Thesensing feedback may further allow processing circuitry to classify thepatient's respiration, e.g., the apneas, as OSA, CSA, or mixed OSA/CSA.In some examples, processing circuitry may further be configured toclassify the patient's respiration as “healthy/normal” based on thesensing feedback, or may determine that the patient's respiration cannotbe classified with a desired degree of confidence, and may turn offtherapy or deliver a default or safety mode therapy, respectively, inresponse to these additional classifications.

As discussed, sleep apnea has two primary manifestations; OSA and CSA.In a general population of patients diagnosed with sleep apnea,approximately 92% will have OSA, approximately 3% will have CSA andapproximately 5% will have MIXED apneas (i.e., the patients will exhibitboth OSA and CSA at different times). For heart failure (HF) patientsdiagnosed with sleep apnea, approximately 54% will have OSA,approximately 6% will have CSA and approximately 40% will have MIXEDapneas. The techniques of this disclosure generally relate to IMD 16delivering CSA, OSA and combination CSA/OSA therapy. Therapy deliverycircuitry 58 (FIG. 5) of IMD 16 may be configured to deliver a firstelectrical stimulation via lead 21. Lead 21 may have a plurality ofelectrodes 30 (FIG. 2). A second electrical stimulation may be deliveredvia lead 20 having a plurality of electrodes 130 (FIGS. 4A and 4B). IMD16 may have processing circuitry 52 (FIG. 5) configured to controltherapy delivery circuitry 58 to deliver the first electricalstimulation configured to treat OSA and control therapy deliverycircuitry 58 to deliver the second electrical stimulation configured totreat CSA. First plurality of electrodes 30 may be located along adistal portion 26 of lead 21 configured to be implanted withinmusculature of a tongue of patient 14. Second plurality of electrodes130 may be located along distal portion 25 of lead 20 configured to beimplanted intravascularly proximate to phrenic nerve(s) 27 withinpatient 14.

As illustrated in FIG. 1, system 10 includes an external device 70,which may be communicatively coupled to IMD 16. External device 70 maybe a computing device, e.g., a hand-held computing device, that providesa user interface for a user to interface with IMD 16. The user may useexternal device 70 to retrieve information from IMD 16 regarding patient14, e.g., diagnostic information regarding one or more conditions ofpatient 14, and/or the performance of IMD 16, e.g., delivery of therapyby the IMD or the condition of components of IMD 16. The user may alsouser external device 70 to program IMD 16, e.g., various sensing,analysis, or therapy parameters of IMD 16. External device 70 may bereferred to as a “programmer” for IMD 16. External device may be asmartphone or tablet. External device 70 may be a local device coupledto IMD 16 by a wireless connection, or a remote device coupled to IMD 16by a network including one or more wired and/or wireless connections.

FIG. 2 is a conceptual diagram of a lead for delivering OSA therapyaccording to one or more examples. Lead 21 may include a flexible,elongated lead body 22 extending from lead proximal end 23 to leaddistal end 26. As illustrated, lead 20 includes one or more electrodes30 carried along a lead distal portion adjacent lead distal end 26 andare configured for insertion within protrusor muscles 42A, 42B, and 46of tongue 40. As one example, the genioglossus muscle includes obliquecompartment 42A and horizontal compartment 42B. In this disclosure, thegenioglossus muscle is referred to as protrusor muscle 42. Protrusormuscle 46 is an example of the geniohyoid muscle.

While protrusor muscles 42 and 46 are described, the example techniquesdescribed in this disclosure are not limited to stimulating protrusormuscles 42 and 46. Also, FIG. 2 illustrates one set of protrusor muscles42 and 46 (e.g., on a first side of tongue 40). The other side of tongue40 also includes protrusor muscles. For instance, a left side of tongue40 includes a first set of protrusor muscles 42 and 46, and a right sideof tongue 30 includes a second set of protrusor muscles.

In some examples, a surgeon may implant one or more leads 21 so one ormore electrodes 30 are implanted within soft tissue, such asmusculature, proximate to medial branches of one or both hypoglossalnerves 11. In some examples, one or more electrodes 30 may beapproximately 5 millimeters (mm) from a major trunk of hypoglossal nerve11. In some examples, one or more electrodes 30 may be placed in an areaof protrusor muscles 42 and 46 including the motor points. This is whereeach nerve axon terminates in the muscle (also called the neuro-muscularjunction). The motor points are not at one location but spread out inthe protrusor muscles. One or more electrodes 30 may be generally in thearea of the motor points so the motor points are within 1 to 10 mm fromone or more electrodes 30. Examples of motor points for protrusormuscles 42 and 46 are illustrated in more detail with respect to FIG. 3.

Tongue 40 includes a distal end, e.g., tip of tongue 40, and electrodes30 may be implanted proximate to the root of tongue 40. The surgeon mayimplant one or more leads 21 so one or more electrodes are implantedproximate to bottom surface 49 of tongue 40, as illustrated in FIG. 2.For example, the location for stimulation for genioglossus muscle 42 maybe approximately 30 mm from the Symphsis of the jaw, e.g., where thegenioglossus and hypoglossal muscles insert. The location forstimulation for geniohyoid muscle 46 may be approximately 40 mm from theSymphsis. For both genioglossus muscle 42 and geniohyoid muscle 44, thelocation for stimulation may be approximately 11 mm lateral to themidline on both the right and left sides of tongue 40 for stimulatingrespective hypoglossal nerves 11. In some examples, rather thanstimulating hypoglossal nerves 11, the examples described in thisdisclosure may be configured for stimulating the motor points, asdescribed in more detail with respect to FIG. 3. Stimulating the motorpoints may result in activation of the hypoglossal nerve 11 but maygenerally be stimulating at a different location than direct stimulationto the hypoglossal nerve 11 trunk or major branches. As a result, insome examples, simulation of one or more motor points may result in moreprecise activation of muscle fibers than may be possible withstimulation of the hypoglossal nerve trunk or major branches itself.

One or more electrodes 30 of lead 21 may be ring electrodes, segmentedelectrodes, partial ring electrodes or any suitable electrodeconfiguration. Segmented and partial ring electrodes each extend alongan arc less than 360 degrees, e.g., 90-120 degrees, around the outerperimeter of lead 21. In this manner, multiple segmented electrodes maybe disposed around the perimeter of lead 21 at the same axial positionof lead 21. In some examples, segmented electrodes may be useful fortargeting different fibers of the same or different nerves at respectivecircumferential positions with respect to lead 21 to generate differentphysiological effects (e.g., therapeutic effects). In some examples,lead 21 may be, at least in part, paddle shaped, e.g., a “paddle” lead,and may include an array of electrodes on a common surface, which may ormay not be substantially flat.

As described above, in some examples, electrodes 30 are withinmusculature of tongue 40. Accordingly, one or more electrodes 30 may be“intramuscular electrodes.” Intramuscular electrodes may be differentthan other electrodes placed on or along a nerve trunk or branch, suchas a cuff electrode, used to directly stimulate the nerve trunk orbranch. The example techniques described in this disclosure are notlimited to intramuscular electrodes and may be extendable to electrodesplaced closer to a nerve trunk or branch of hypoglossal nerve(s) 11.Also, in some examples, rather than one or more electrodes 30 being“intramuscular electrodes,” one or more electrodes 30 may be implantedin connective tissue or other soft tissue proximate to hypoglossal nerve11.

In some examples, lead 21 may be configured for advancement through thesoft tissue, which may include the protrusor muscle tissue, to anchorelectrodes 30 in proximity of the hypoglossal nerve(s) innervatingprotrusor muscles 42 and/or 46, and/or motor points connecting axons ofhypoglossal nerve(s) to respective muscle fibers of protrusor muscles 42and/or 46. However, in some examples, lead 21 may be configured foradvancement through vasculature of tongue 40. As one example, a surgeonmay implant lead 21 in the lingual veins near hypoglossal nerve 11though venous access in the subclavian vein. In such examples, one ormore electrodes 30 may be “intravascular electrodes.”

As described above, electrical stimulation therapy generated by IMD 16and delivered via one or more electrodes 30 may activate protrusormuscles 42 and 46 to move tongue 40 forward, to promote a reduction inobstruction or narrowing of the upper airway 48 during sleep. As usedherein, the term “activated” with regard to the electrical stimulationof protrusor muscles 42 and 46 refers to electrical stimulation causingdepolarization or an action potential of the cells of the nerve. e.g.,hypoglossal nerve(s) 11, or stimulation at the neuro-muscular junctionbetween the nerve and the protrusor muscles, e.g., at the motor points,innervating protrusor muscles 42 and 46 and motor points and subsequentdepolarization and mechanical contraction of the protrusor muscle cellsof protrusor muscles 42 and 46. In some examples, protrusor muscles 42and 46 may be activated directly by the electrical stimulation therapy.

Protrusor muscles 42 and/or 46, on a first side of tongue 40, e.g., leftor right side of tongue 40), may be activated by a medial branch of afirst hypoglossal nerve 11, and the protrusor muscles, on a second sideof tongue 40, e.g., other of left or right side of tongue 40), may beactivated by a medial branch of a second hypoglossal nerve. The medialbranch of a hypoglossal nerve 11 may also be referred to as the XIIthcranial nerve. The hyoglossus and styloglossus muscles (not shown inFIG. 2), which cause retraction and elevation of tongue 40, areactivated by a lateral branch of hypoglossal nerve 11.

One or more electrodes 30 may be used to deliver bilateral or unilateralstimulation to protrusor muscles 42 and 46 via the medial branch of thehypoglossal nerve or branches of hypoglossal nerve 11, e.g. such as atthe motor point where a terminal branch of the hypoglossal nerveinterfaces with respective muscle fibers of protrusor muscles 42 and/or46. For example, one or more electrodes 30 may be coupled to outputcircuitry of IMD 16 to enable delivery of electrical stimulation pulsesin a manner selectively activating the right and left protrusor musclesin a cyclical or alternating pattern to avoid muscle fatigue whilemaintaining upper airway patency. Additionally, or alternatively, IMD 16may deliver electrical stimulation to selectively activate protrusormuscles 42 and/or 46, or portions of protrusor muscles 42 and/or 46,during unilateral stimulation of the left or right protrusor muscles.

For instance, in some examples, one lead 21 may be implanted so one ormore of electrodes 30 deliver electrical stimulation to stimulate theleft hypoglossal nerve or motor points of protrusor muscles on the leftside of tongue, and therefore cause the left protrusor muscles toactivate. In such examples, the electrical stimulation from one or moreelectrodes 30 may not be of sufficient amplitude to stimulate the righthypoglossal nerve or motor points of protrusor muscles on the right sideof tongue and cause the right protrusor muscles to activate. In someexamples, one lead 21 may be implanted so one or more of electrodes 30deliver electrical stimulation to stimulate the right hypoglossal nerveor motor points of protrusor muscles on the right side of tongue, andtherefore cause the right protrusor muscles to activate. In suchexamples, the electrical stimulation from one or more electrodes 30 maynot be of sufficient amplitude to stimulate the left hypoglossal nerveor motor points of protrusor muscles on the left side of tongue andcause the left protrusor muscles to activate. Accordingly, in someexamples, an adaptor may be used to apply two leads like lead 21 tostimulate each of the left and right hypoglossal nerves.

In some examples, one lead 21 may be implanted substantially in themiddle (e.g., center) of tongue 40. In such examples, one or moreelectrodes 30 may deliver electrical stimulation to both hypoglossalnerves or motor points of both muscles on the both sides of tongue 40causing both hypoglossal nerves or motor points to activate respectiveleft and right protrusor muscles. It may be possible to utilize currentsteering and field shaping techniques so one or more electrodes 30deliver a first electrical stimulation stimulating the left hypoglossalnerve or motor points of protrusor muscles on the left side of tongue 40with little to no stimulation of the right hypoglossal nerve or motorpoints of protrusor muscles on the right side of tongue, and then one ormore electrodes 30 deliver a second electrical stimulation stimulatingthe right hypoglossal nerve or motor points of protrusor muscles on theright side of tongue with little to no stimulation of the lefthypoglossal nerve or motor points of protrusor muscles on the left sideof tongue. In examples where two leads like lead 21 are utilized, eachlead may alternate delivery of stimulation to respective hypoglossalnerves or motor points. In this way, IMD 16 may stimulate onehypoglossal nerve 11 or one set of motor points and then the otherhypoglossal nerve or another set of motor points, which may reducemuscle fatigue.

For instance, continuous stimulation may cause protrusor muscles to becontinuously in a protruded state. This continuous contraction may causeprotrusor muscles 42 and/or 46 to fatigue. In such cases, due tofatigue, the stimulation may not cause protrusor muscles 42 and/or 46 tomaintain a protruded state (or higher intensity of the electricalstimulation may be needed to cause protrusor muscles 42 and/or 46 in theprotruded state). By stimulating one set of protrusor muscles, e.g.,left or right, a second set, e.g., other of left or right, of protrusormuscles may be at rest. Stimulation may then alternate to stimulate theprotrusor muscles that were at rest and thereby maintain protrusion oftongue 40, while permitting the protrusor muscles 42 and/or 46 that werepreviously activated to rest. Hence, by cycling between alternatestimulation of the left and right protrusor muscles, tongue 40 mayremain in the protruded state, while one of the first or second set ofprotrusor muscles is at rest. In some examples, one lead 21 may beimplanted laterally or diagonally across tongue 40 so some of electrodes30 may be used to stimulate the left hypoglossal nerve 11 and/or motorpoints of the protrusor muscles on the left side of tongue 40 and someof electrodes 30 may be used to stimulate the right hypoglossal nerveand/or motor points of the protrusor muscles on the right side of tongue40. In such examples, IMD 16 may selectively deliver electricalstimulation to a first hypoglossal nerve and/or first motor points ofthe protrusor muscles on the a first side of tongue 40 via a first setof one or more electrodes 30, and then deliver electrical stimulation toa second hypoglossal nerve and/or/or second set of motor points of theprotrusor muscles on a second side of tongue 40 via a second set of oneor more electrodes 30. This may be another way in which to reduce musclefatigue. Additional methods to reduce muscle fatigue include waveformvariations, e.g., rectangle, sawtooth, triangle, or biphasic, and/or anytechnique to manipulate the electrical field to vary recruitment ofnerve fibers.

Lead proximal end 24 includes a connector (not shown in FIG. 2) coupledto connector assembly 17 of IMD 16 to provide electrical connectionbetween circuitry enclosed by housing 15 of IMD 16. Elongated lead body22 encloses electrical conductors extending from each of one or moreelectrodes 30 to the proximal connector at proximal end 24 to provideelectrical connection between output circuitry of IMD 16 and theelectrodes 30.

There may be various ways in which lead 21 is implanted in patient 14.As one example, a surgeon may insert a needle (also called introducerneedle) through below the jaw and in tongue 40 starting from the back oftongue 40. The surgeon may insert the needle until the needle reachesproximate to the tip of tongue 40, angling the needle to be proximate tothe hypoglossal nerve 11, e.g., left or right hypoglossal nerve 11, andto the motor points. In some examples, the needle may include one ormore electrodes at the distal end, and the surgeon may cause the one ormore electrodes of the needle to output an electrical stimulation, whichin turn causes a physiological response such as activation of protrusormuscles 42 and/or 46 and protrusion of tongue 40. The surgeon may adjustthe location of the needle based on the physiological response todetermine a location in tongue 40 providing effective treatment. Using aneedle with stimulating electrodes is not necessary in every example.

Once the needle is in place, the surgeon may insert a guidewire (orsimply “guide”) through the needle and anchor the guidewire to tissue oftongue 40. Then, the surgeon may remove the needle.

The surgeon may place an introducer, which may or may not include adilator, over the guidewire through the opening created by the needle.The introducer may be referred to as an introducer, introducer sheath,or introducer/dilator. In some examples, the introducer may optionallyinclude one or more electrodes the surgeon may use to stimulate tongue40 to ensure lead 21 will be located in the correct location, relativeto the target nerve tissue. e.g., motor points. Once the introducer isin place, the surgeon may remove the guidewire. In some examples, theintroducer may be flexible or curved to ease placement of the introducerin patient 14.

The surgeon may put lead 21 through the introducer so one or moreelectrodes 30 are proximate to hypoglossal nerve 11 (e.g., so distal end26 is near tip of tongue as one non-limiting example). Electrodes 30 maybe proximate to hypoglossal nerve 11 and/or motor points of theprotrusor muscles due to the needle creating an opening near hypoglossalnerve 11 and/or motor points of the protrusor muscle. The surgeon maythen tunnel proximal end 24 of lead 21 back to a connection with IMD 16.

In this manner, the surgeon may implant one lead 21. In examples wheretwo or more leads are implanted, the surgeon may perform steps similarto those described above.

FIG. 1 illustrates the location of IMD 16 as being in the left or rightpectoral region. For instance, the surgeon may plan on implanting IMD 16in the left pectoral region unless another medical device is alreadyimplanted in the left pectoral region. The surgeon may then implant IMD16 in the right pectoral region. There may be other locations where thesurgeon may implant IMD 16 such as the back of patient 14. The exampletechniques are not limited to any particular implant location of IMD 16.Further, an adaptor may be used to provide for two leads, e.g.,positioned bilaterally, which may be positioned in a right and left sideof the patient's hypoglossal nerve 11, protrusor muscles 42 and/or 46 orone or more motor points 54A, 54B, 55A and/or 55B.

Elongated lead body 22 may be a flexible lead body through whichinsulated electrical conductors extend to respective electrodes 30. Thedistal most electrode 30 may be adjacent or proximate to lead distal end26. Each of electrodes 30 may be spaced proximally from the respectiveadjacent one of electrodes 30 by respective interelectrode distances.

In some examples, housing 15 of IMD 16 may include an electrodefunctioning as a cathode or anode as part of a cathode/anode pair withone of electrodes 30. In some examples, housing 15 itself may functionas the cathode or anode.

Each of electrodes 30 is a circumferential ring electrode which may beuniform in diameter with elongated lead body 22. As described above,electrodes 30 may include other types of electrodes such as a tipelectrode, e.g., electrode 130A (FIG. 4A), a helical electrode, e.g.,electrode 130D (FIG. 4B), a coil electrode, a segmented electrode, or abutton electrode as examples.

Lead 21 may include one or more fixation members 32 for minimizing thelikelihood of lead migration. Fixation member 32 may include multiplesets of tines which engage the surrounding tissue when lead distalportion 28 is positioned at the target therapy delivery site. Tines offixation member 32 may extend radially and proximally at an anglerelative to a longitudinal axis of lead body 22 to prevent or reduceretraction of lead body 22. Tines of fixation member 32 may becollapsible against elongated lead body 22 when lead 21 is held withinthe confines of a lead delivery tool, e.g., a needle or introducer, usedto deploy lead distal portion 26 at the target implant site. In someexamples, fixation member 32 may additionally or alternatively includeone or more hooks, barbs, helices, or other fixation mechanismsextending from one or more longitudinal locations along elongated leadbody 22 and/or lead distal end 26. Additional fixation techniques mayincorporate the use of bioabsorbable coatings, e.g., sucrose, alginate,etc., when used after acute implantation, dissolve away so as to exposethe anchoring feature, e.g., hooks, barbs, helices, micro-needlesurfacing, or other fixation mechanisms.

Fixation members 32 may partially or wholly engage one or more ofprotrusor muscles 42 and/or 46, one or more motor points 54A, 54B, 55Aand/or 55B, and/or other muscles below tongue 40, and/or other softtissues of the neck, e.g., fat and connective tissue, when proximal endof lead body 22 is tunneled to an implant pocket of IMD 16. In someexamples, fixation member 32 may include one or more fixation mechanismslocated at other locations, including at or proximate to distal end 26,between electrodes 30, or otherwise more distally or more proximallythan the location shown in FIG. 2.

The implant pocket of IMD 16 may be in a pectoral region of patient 14.Accordingly, the length of lead body 22 from distal portion 26 to leadproximal end 24 may be selected to extend from a target therapy deliverysite in protrusor muscles 42 and/or 46 to a location in the pectoralregion where IMD 16 is implanted. The length may be up to 10 centimeters(cm) or up to 20 cm as examples but may generally be 25 cm or less,though longer or shorter lead body lengths may be used depending on theanatomy and size of patient 14.

In some examples, an IMD 16 having a lead 21 with a proximal end 24 anda distal end 26 defines lead body 22 with electrodes 30 disposed on lead21. In other examples, a fixation member 32 may be disposed on lead body22 of lead 21. Fixation member 32 may be configured to secure lead 21 totissue within a patient 14. Fixation member 32 may be disposed on lead21 at a location proximal to electrodes 30 of lead 21.

FIG. 3 is a conceptual diagram illustrating example locations of motorpoints where stimulation for OSA therapy may be delivered. FIG. 3illustrates jaw 50 of patient 14, where patient 14 is in a supineposition and jaw 50 of patient 14 is viewed from an inferior location ofpatient 14. For instance, FIG. 3 illustrates symphysis 51 and hyoid bone52. In the example illustrated in FIG. 3, the line interconnectingsymphysis 51 and hyoid bone 52 may be considered as a y-axis along themidline of tongue 40. FIG. 3 also illustrates intergonial distance 53between the two gonia of patient 14, where the gonia is a point on eachside of the lower jaw 50 at the mandibular angle. Intergonial distance53 may be along the x-axis of tongue 40.

FIG. 3 illustrates motor points 54A and 54B and motor points 55A and55B. Motor points 54A may be motor points for the right genioglossusmuscle, and motor points 54B may be motor points for the leftgenioglossus muscle. Motor points 55A may be motor points for the rightgeniohyoid muscle, and motor points 55B may be motor points for the leftgeniohyoid muscle. Motor points 54A and 54B and motor points 55A and 55Bmay genericize the motor points for each muscle for purposes ofillustration. There may be additional motor points and/or motor pointsat different locations for each muscle.

In one or more examples, lead 21 and/or one or more electrodes 30 may beimplanted proximate to motor points 54A, 54B, 55A, or 55B forstimulating at motor points 54A, 54B, 55A, and/or 55B. For instance, inexamples where two leads are implanted, a first lead and its electrodesmay be implanted proximate to motor points 54A and/or 55A and a secondlead and its electrodes may be implanted proximate to motor points 54Band/or 55B. In one or more examples, electrodes 30 may be approximately1 mm to 10 mm from respective motor points 54A, 54B, 55A, or 55B.

A hypoglossal nerve 11, e.g., on the left or right side of tongue 40,initially is a trunk of nerves fibers called axons. The axons ofhypoglossal nerve 11 branch out. For example, the trunk of hypoglossalnerve 11 includes multiple sets of axons including a first set of axons,and the first set of axons branch out from the trunk of hypoglossalnerve 11. The first set of axons include multiple groups of axonsincluding a first group of axons, and the first group of axons branchout from the first set of axons, and so forth. The locations where thebranched-out axons interface with respective muscle fibers of protrusormuscles 42 and/or 46, e.g., genioglossus and/or geniohyoid muscle, arereferred to as motor points.

For instance, a branch of hypoglossal nerve 11 interfacing, e.g.,connects at the neuro-muscular junction, with the muscle fiber isreferred to as a terminal branch, and the end of the terminal branch isa motor point. The length of a terminal branch may be approximately 10mm from hypoglossal nerve 11 to the genioglossal or geniohyoid muscles.In some examples, there may be approximately an average of 1.5 terminalbranches with a standard deviation of ±0.7 for the right geniohyoidmuscle, an average of 4.8 terminal branches with a standard deviation of±1.4 for the right genioglossus muscle, an average of 2.0 terminalbranches with a standard deviation of ±0.9 for the left geniohyoidmuscle, and an average of 5.1 terminal branches with a standarddeviation of ±1.9 for the left genioglossus muscle.

There may be possible advantages with stimulating at motor points 54A,54B, 55A, or 55B, as compared to some other techniques. For instance,some techniques utilize cuff electrodes or stimulate at hypoglossalnerve 11. Due to the different bifurcation patterns, placing a cuffelectrode around hypoglossal nerve 11, or generally attaching anelectrode to hypoglossal nerve 11 may be challenging. Also, where cuffelectrodes or electrodes attach to hypoglossal nerve 11 are used,implanting electrodes around or at each of hypoglossal nerves 11requires multiple surgical entry points to attached to both hypoglossalnerves. Moreover, utilizing cuff electrodes or electrodes attaching tohypoglossal nerves 11 may possibly negatively impact the nerve bytugging, stretching, or otherwise causing irritation. Accordingly,utilizing lead 21 and electrodes 30 implanted proximate to the motorpoints may be beneficial, e.g., less surgery to implant and less impacton the nerve, as compared to techniques where cuff electrodes orelectrodes implanted on the hypoglossal nerve are utilized. Anotherdisadvantage of using a cuff is that the nerve trunk locations which maybe practically accessed surgically to implant the cuff often includenerve branches going to the retrusor muscles, which when activated maymove the tongue in the wrong direction closing the airway instead ofopening.

Furthermore, stimulating at motor points 54A, 54B, 55A, and/or 55B, suchas at the bifurcation point of a motor neuron attaching to musclefibers, may provide advantages such as for better control of musclemovement. Because motor points 54A, 54B, 55A, and 55B are spatiallydistributed, by stimulating motor points 54A, 54B, 55A, and/or 55B, theamount of the genioglossus and geniohyoid muscle being stimulated may becontrolled. Also, stimulating at motor points 54A, 54B, 55A, and/or 55Bmay allow for more gentle muscle activation. For instance, whenstimulation is provided near the trunk of hypoglossal nerve 11 or bothmotor points 54A and 54B and/or motor points 55A and 55B, evenstimulation signal with relatively small amplitude may cause thegenioglossus and/or geniohyoid muscle to fully protrude, e.g., there ishigh loop gain where small stimulation amplitudes cause large muscleprotrusion. Fine tuning of how much to protrude the genioglossus and/orgeniohyoid muscle may not be available when stimulating at a trunk ofhypoglossal nerve 11 or both motor points 54A and 54B and/or motorpoints 55A and 55B. However, there may be lower loop gain stimulating atmotor points 54A, 54B, 55A, and/or 55B. For instance, a stimulationsignal having a lower amplitude may move causing the genioglossus and/orgeniohyoid muscle to protrude a small amount, and a stimulation signalhaving a higher amplitude may move causing the genioglossus and/orgeniohyoid muscle to protrude a higher amount when stimulating at motorpoints 54A, 54B, 55A and/or 55B.

The following are example locations of motor points 54A, 54B, 55A, and55B relative to the midline (x-axis), posterior symphysis 51 (y-axis),and depth (z-axis), where the depth is from the plane formed by theinferior border of symphysis 51 and anterior border of hyoid bone 52.

Motor points 54A may be for the right genioglossus muscle and may belocated at 13.48 mm±3.59 from the x-axis, 31.01 mm±6.96 from the y-axis,and 22.58 mm±3.74 from the z-axis. Motor points 55A may be for the rightgeniohyoid muscle and may be located at 11.74 mm±3.05 from the x-axis,41.81 mm±6.44 from the y-axis, and 16.29 mm±3.40 from the z-axis. Motorpoints 54B may be for the left genioglossus muscle and may be located at9.96 mm±2.24 from the x-axis, 29.62 mm±9.25 from the y-axis, and 21.11mm±4.10 from the z-axis. Motor points 55B may be for the left geniohyoidmuscle and may be located at 11.45 mm±1.65 from the x-axis, 39.63mm±8.03 from the y-axis, and 15.09 mm±2.41 from the z-axis.

FIGS. 4A and 4B are conceptual diagrams respectively illustratingexample electrical leads 20A and 20B (collectively, “electrical leads20”) that may be used for stimulation of the phrenic nerve in deliveringCSA therapy. As illustrated in FIGS. 4A and 4B, electrical leads 20A and20B may respectively have electrodes 130A, 130B, and 130C, andelectrodes 130D and 130E (collectively, “electrodes 130”) alongrespective distal portions 25A and 25B (collectively, “distal portions25”). Distal portions 25 of leads 20 are configured to be implantedintravascularly proximate to phrenic nerve(s) 27 within the patient 14.Electrical lead 20A may have fixation mechanism 135 along the length oflead body 22 or another fixation mechanism (not shown) near electrode130A. Electrode 130D of electrical lead 20B has a helical configurationwhich may be used for fixation. Other fixation mechanisms may includefixation screws capable of retracting into and extending from lead body22. This type of mechanism may be retracted when lead 20 is passedthrough the vasculature to avoid unintended interactions between themechanism and patient tissue. Another example fixation configuration maybe any mechanical configuration used to increase the outside diameter ofthe lead to wedge the lead into place.

In general, leads 20 are described as being delivered vascularly to aposition proximate to the phrenic nerve. In some examples, however, alead 20 configured to stimulate the phrenic nerve may be placed near thephrenic nerve by percutaneous methods, e.g., similar to lead 21discussed above.

In some examples, electrodes 130 may be used as unipolar electrodes toprovide stimulation and/or for sensing in connection with an electrode(e.g., housing 15) on IMD 16. In some examples, two or more ofelectrodes 130 may be used together, e.g., as bipolar electrodes, eachof electrodes 130 providing stimulation and/or sensing electricalsignals in connection with another electrode 130 on a lead 20. In theexample illustrated by FIG. 4A, electrodes 130B and 130C may provide arelatively more closely spaced bipolar pair of electrodes as compared toeither of electrodes 130B and 130C with electrode 130A, which may beused for delivery of electrical stimulation to the phrenic nerve and/orsensing electrical signals. In some examples, leads 20 may include moreelectrodes 130, fewer electrodes 130, or different arrangements ofelectrodes 130 on leads 20.

In some examples, IMD 16 senses electrical signal via electrodes 130,electrodes 30, one or more electrodes on housing 15, and/or otherelectrodes. For example, IMD 16 may electrical signals attendant to thedepolarization and repolarization of the heart, e.g., a cardiacelectrogram (EGM) or electrocardiogram (ECG). As another example, IMD 16may sense a bioimpedance or other impedance, such as a thoracicimpedance or impedance of tissue proximate to a pair of electrodes. Insome examples, IMD 16 may be configured to sense various signalsattendant to the activation of diaphragm 90 (FIG. 1) in response toelectrical stimulation to phrenic nerve(s) 27. IMD 16 may also includeor be coupled to other sensors, such as one or more accelerometers fordetecting other physiological parameters of a patient, such as activityor posture.

Electrical lead 20 may include one or more fixation mechanisms, e.g.,active and/or passive, to provide stability of the locations ofelectrodes 130, e.g., for stimulation of phrenic nerve(s) 27. In theillustrated examples, leads 20 includes active fixation mechanisms 130Dand 135 provided at distal portions 25 of leads 20. Active fixationmechanisms 130D and 135 and/or leads 20 may be rotated when electrodes130 are located at a desired position to cause the active fixationmechanisms to pierce and become fixedly engaged with adjacent tissue,substantially precluding further movement of leads 20 and/or electrodes130.

Techniques for stimulating one or more of phrenic nerve(s) 27 areprimarily described herein as being performed by IMD 16, e.g., by aprocessing circuitry 57 (FIG. 5) of IMD 16. For example, IMD 16 mayprocess respiratory-based signals to determine whether the IMD 16 shouldcontinue to deliver phrenic nerve stimulation based on currentparameters, or whether adjustments to the parameters should be made.Processing circuitry 57 in IMD 16 may also control which of OSA and CSAtherapy IMD 16 delivers at any given time, and the parameters used byIMD 16 to deliver therapy.

FIG. 5 is block diagram illustrating example configurations ofimplantable medical devices (IMDs) which may be utilized in the systemof FIG. 1. As shown in FIG. 5, IMD 16 includes sensing circuitry 56,processing circuitry 57, therapy delivery circuitry 58, switch circuitry59, memory 60, telemetry circuitry 61, and power source 62. IMD 16 mayinclude a greater or fewer number of components. IMD 16 may be used forchronic stimulation, but an external medical device may also be used fortrialing, which may be similar to IMD 16, but need not necessarily besimilar to IMD 16.

In the illustrated examples, IMD 16 is coupled to a plurality ofelectrodes 230A-230N (collectively, “electrodes 230”). Electrodes 230may include electrodes 30 (FIG. 2), electrodes 130 (FIG. 4), one or moreelectrodes on housing 15 of IMD 16 (FIG. 1), and/or other electrodeselectrically coupled to IMD 16. Switch circuitry 59 may be configuredto, in response to instructions from processing circuitry 57, switch thecoupling of electrodes 230 between sensing circuitry 56 and therapydelivery circuitry 58. IMD 16 may include switch circuitry 59 such as toselectively connect and disconnect electrodes 230 from therapy deliverycircuitry 58, e.g., depending on which, if any of OSA and CSA therapyare delivered at a given time.

In some examples, IMD 16 may include one or more sensors configured tosense posture or position of patient 14. For example, IMD 16 may includeone or more accelerometers, such as a 3-axis accelerometer 84, todetermine a posture of patient 14. Accelerometer 84 may sense motionassociated with respiration. Processing circuitry 57 may use a signalproduced by accelerometer 84 to sense, “healthy/normal” respirations,apnea event, and features of the respiration signal by which apneaevents may be classified as OSA, CSA, or mixed OSA/CSA.

Sensing circuitry 56 may also include circuitry to detect a cardiacelectrical signal, such as a cardiac EGM and/or an ECG, via a selectedtwo or more of electrodes 230. In the illustrated example, sensingcircuitry 56 includes ECG sensing circuitry 82, which may be used tosense a subcutaneous ECG, as well as to detect depolarization and/ormorphological features in the ECG. In addition, since the ECG signalproduced by ECG sensing circuitry 82 may vary based on respiration ofthe patient, ECG sensing circuitry 82 may be used to detect respiration,including apnea events and features of a respiration signal by whichapnea events may be classified as “healthy/normal”, OSA, CSA, or mixedOSA/CSA.

Sensing circuitry 56 may also include impedance sensing circuitry 86configured to measure impedance using two or more of electrodes 230.Impedance sensing circuitry 86 may detect thoracic impedance and/ortissue impedance, as examples. Since such impedances may vary based onpatient respiration, impedance sensing circuitry 86 may also be used todetect respiration, including apnea events and features of a respirationsignal by which apnea events may be classified as “healthy/normal”, OSA,CSA, or mixed OSA/CSA.

Sensing circuitry 56 may include a variety of additional or alternativecircuitry for sensing a respiration signal, or other signals indicativeof apnea or useful for distinguishing between “healthy/normal”, OSA,CSA, and mixed OSA/CSA respiration. For example, movement sensed byaccelerometer 84 or another motion sensor may indicate if patient 14 ishaving restless sleep, which may be indicative of the onset of OSA. Asanother example, sensing circuitry 56 may include acoustical sensors ora microphone for detecting vibrations in upper airway 48. Vibrations inupper airway 48 may be indicative of the onset of OSA. In some examples,sensing circuitry 56 may be configured to sense electromyogram (EMG)signals via two or more of electrodes 230. Sensing circuitry 56 may beswitchably coupled to electrodes 230, e.g., electrodes 30 of FIG. 1, viaswitch circuitry 59 to be used as EMG sensing electrodes when electrodes230 are not being used for stimulation. Processing circuitry 57 may useEMG signals to detect sleep state and/or low tonal state of protrusormuscles 42 and/or 46 for use in detecting OSA and delivering electricalstimulation configured to treat OSA.

Sensing circuitry 56 may include any of a variety of components forsensing any of the signals described herein. For example, sensingcircuitry 56 may include amplifiers, filters, sample and hold circuitry,and/or other circuitry configured to condition a signal and sensefeatures of the signal. In some examples, sensing circuitry 56 mayinclude analog-to-digital conversion circuitry to provide digitizedversions of signals to processing circuitry 57 for analysis, e.g., asdescribed herein.

In general, IMD 16 may comprise any suitable arrangement of hardware,alone or in combination with software and/or firmware, to perform thetechniques attributed to IMD 16 and processing circuitry 57, therapydelivery circuitry 58, and telemetry circuitry 61 of IMD 16. In variousexamples, IMD 16, e.g., processing circuitry 57, may include one or moreprocessors, such as one or more microprocessors, digital signalprocessors (DSPs), application specific integrated circuits (ASICs),field programmable gate arrays (FPGAs), or any other equivalentintegrated or discrete logic circuitry, as well as any combinations ofsuch components. IMD 16 also, in various examples, may include a memory60, such as random access memory (RAM), read only memory (ROM),programmable read only memory (PROM), erasable programmable read onlymemory (EPROM), electronically erasable programmable read only memory(EEPROM), flash memory, comprising executable instructions for causingthe one or more processors to perform the actions attributed to them.Moreover, although sensing circuitry 56, processing circuitry 57,therapy delivery circuitry 58, switch circuitry 59, and telemetrycircuitry 61 are described as separate circuitry, in some examples,sensing circuitry 56, processing circuitry 57, therapy deliverycircuitry 58, switch circuitry 59, and telemetry circuitry 61 arefunctionally integrated. In some examples, sensing circuitry 55,processing circuitry 57, therapy delivery circuitry 58, switch circuitry59, and telemetry circuitry 61 correspond to individual hardware units,such as ASICs, DSPs, FPGAs, or other hardware units.

Memory 60 stores therapy programs 63 specifying stimulation parametervalues for the electrical stimulation provided by IMD 16. Memory 60 mayalso store instructions for execution by processing circuitry 57, inaddition to stimulation programs 63. For example, memory 60 may storevarious instructions, as well as thresholds or other parameters, used byprocessing circuitry 57 for sensing respiration and apnea events, anddistinguishing between “healthy/normal”, OSA, CSA, and OSA/CSA.Information related to sensed parameters of patient 14, e.g., fromsensing circuitry 56 or the one or more sensors of IMD 16, may berecorded for long-term storage and retrieval by a user, and/or used byprocessing circuitry 57 for adjustment of stimulation parameters, e.g.,amplitude, pulse width, and pulse rate. In some examples, memory 60includes separate memories for storing instructions, electrical signalinformation, and stimulation programs 62. In some examples, processingcircuitry 57 may select new stimulation parameters for a stimulationprogram 62 or new stimulation program from stimulation programs 62 touse in the delivery of the electrical stimulation based on patient inputand/or monitored physiological states after termination of theelectrical stimulation.

Generally, therapy delivery circuitry 58 generates and deliverselectrical stimulation under the control of processing circuitry 57. Insome examples, processing circuitry 57 controls therapy deliverycircuitry 58 by accessing memory 60 to selectively access and load atleast one of stimulation programs 62 to therapy delivery circuitry 58.For example, in operation, processing circuitry 57 may access memory 60to load one of stimulation programs 62 to therapy delivery circuitry 52.

By way of example, processing circuitry 57 may access memory 60 to loadone of stimulation programs 62 to therapy delivery circuitry 58 fordelivering the electrical stimulation to patient 14. A clinician orpatient 14 may select a particular one of stimulation programs 62 from alist using a programming device, such as a patient programmer or aclinician programmer. Processing circuitry 57 may receive the selectionvia telemetry circuitry 61. Therapy delivery circuitry 58 delivers theelectrical stimulation to patient 14 according to the selected programfor an extended period of time, such as minutes or hours while patient14 is asleep, e.g., as determined from the one or more sensors and/orsensing circuitry 56. For example, processing circuitry 57 may controlswitch circuitry 59 to couple electrodes 30 to therapy deliverycircuitry 58.

Therapy delivery circuitry 58 delivers electrical stimulation accordingto stimulation parameters. In some examples, therapy delivery circuitry58 delivers electrical stimulation in the form of electrical pulses. Insuch examples, relevant stimulation parameters may include a voltageamplitude, a current amplitude, a pulse rate, a pulse width, a dutycycle, or the combination of electrodes 30 therapy delivery circuitry 58uses to deliver the stimulation signal. In some examples, therapydelivery circuitry 58 delivers electrical stimulation in the form ofcontinuous waveforms. In such examples, relevant stimulation parametersmay include a voltage or current amplitude, a frequency, a shape of thestimulation signal, a duty cycle of the stimulation signal, or thecombination of electrodes 30 therapy delivery circuitry 58 uses todeliver the stimulation signal.

In some examples, the stimulation parameters for the stimulationprograms 62 may be selected to cause protrusor muscles 42 and/or 46 to aprotruded state, e.g., to open-up airway 48. An example range ofstimulation parameters for the electrical stimulation likely to beeffective in treating OSA, e.g., upon application to hypoglossal nerves11 or both motor points 54A and 54B and/or motor points 55A and 55B, areas follows:

1. Frequency or pulse rate: between about 30 Hz and about 50 Hz, such asabout 40 Hz. In some examples, the minimum target frequency is usedwhich may achieve muscle tetany, e.g., constant contraction, and theprovide the required force to open the airway.

2. Amplitude: between about 0.5 milliamps (mA) and about 3 mA, withaverage of approximately 1.5 mA. The maximum amplitude may beapproximately 10 mA. In some examples, bilateral stimulation may bedelivered with the same or different amplitudes for the left and rightsides of the patient, such as 1.3 mA for the left side, and 1.5 mA forthe right side.

3. Pulse Width: between about 100 microseconds (μs) and about 500 μs. Insome examples, a pulse width of 150 μs might be used for minimal powerconsumption. In some examples, the pulse width is 210 μs. In some cases,shorter pulse widths may result in higher current or voltage amplitudes.In yet other cases, pulse shape waveform variations such as rectangle,sawtooth, triangle, monophasic, biphasic, etc. and/or any technique tomanipulate the electrical field to vary recruitment of nerve fibers.

In some examples, higher amplitudes or longer pulse duration mayincrease movement of tongue 40 by recruiting additional motor units. Apulse width of typically 200 μs evokes most large and small musclefiber/motor units for near-maximal effect. Shorter pulse widths such asless than or equal 200 μs may recruit the largest most fatigue-resistantmuscle fibers. Long-pulse duration such as greater than 200 μs mayrecruit large motor fibers and the smallest fast fatiguing musclefibers. Titrating the pulse width duration may be used to minimizerecruitment fatigue sustaining maximal clinical movement effect over thetreatment period.

Processing circuitry 57 may select therapy programs 63 for alternatingdelivery of electrical stimulation between stimulating left protrusormuscles 42 and/or 46 and right protrusor muscles 42 and/or 46, such asin examples where two leads 20 are implanted. In some examples, theremay be some overlap in the delivery of electrical stimulation so forsome of amount of time both left and right protrusor muscles 42 and/or46 are being stimulated. In some examples, there may be a pause inalternating stimulation (e.g., stimulate left protrusor muscles, a timeperiod with no stimulation, then stimulate right protrusor muscles, andso forth). Processing circuitry 50 may also select stimulation programs62 selecting between different combinations of electrodes 30 forstimulating, such as to stimulate different locations of hypoglossalnerve(s) 11 or both motor points 54A and 54B and/or motor points 55A and55B, which may help with fatigue as well as provide more granularcontrol of how much to protrude tongue 40.

In some examples, therapy delivery circuitry 58 drives electrodes 30 oflead 21 for treatment of OSA, and electrodes 130, 130A of lead 20 fortreatment of CSA. Specifically, therapy delivery circuitry 58 maydeliver electrical stimulation to tissue of patient 14 via selectedelectrodes 30 carried by lead 21 and selected electrodes 130, 130Acarried by lead 20. The electrical stimulation delivered via electrodes130 to treat CSA may be, in at least some aspects similar to cardiacpacing, and may be referred to as phrenic pacing. Example parameters forCSA stimulation may be as follows:

Frequency or pulse rate: between about 10 Hz and 100 Hz, such as about60 Hz.

Amplitude: between about 0 mA and 10 mA, such as about 8.1 mA.Stimulation amplitude may be varied in a sinusoidal pattern, e.g.,corresponding to a normal respiration rate for an adult at rest of 12 to20 breaths per minute. Typically, the inhalation/exhalation ratio is1:2, i.e., twice the amount of time in the exhalation phase than theinhalation phase. With such a ration, a four second breath cycle (15breaths per min) will break down to 1.33 seconds of inspiration and 2.66second of expiration. In some examples, stimulation is only appliedduring inspiration in a ramping pattern to produce a smooth diaphragmcontraction. During expiration the stimulation may be turned off and thediaphragm 90 relaxes.

-   -   Pulse Width: between about 60 microseconds (usec) and 1,000        usec, such as about 500 usec.

In some examples, processing circuitry 57 may control therapy deliverycircuitry 58 to deliver or terminate the electrical stimulation based onpatient input received via telemetry circuitry 61. Telemetry circuitry61 includes any suitable hardware, firmware, software or any combinationthereof for communicating with another device, such as an externaldevice. Under the control of processing circuitry 57, telemetrycircuitry 61 may receive downlink telemetry, e.g., patient input, fromand send uplink telemetry, e.g., an alert, to a programmer with the aidof an antenna, which may be internal and/or external. Processingcircuitry 57 may provide the data to be uplinked to the programmer andthe control signals for telemetry circuitry 61 and receive data fromtelemetry circuitry 61.

Generally, processing circuitry 57 controls telemetry circuitry 61 toexchange information with a medical device programmer and/or anotherdevice external to IMD 16. Processing circuitry 57 may transmitoperational information and receive stimulation programs or stimulationparameter adjustments via telemetry circuitry 61. Also, in someexamples, IMD 16 may communicate with other implanted devices, such asstimulators, control devices, or sensors, via telemetry circuitry 61.

Power source 62 delivers operating power to the components of IMD 16.Power source 62 may include a battery and a power generation circuit toproduce the operating power. In some examples, the battery may berechargeable to allow extended operation. Recharging may be accomplishedthrough proximal inductive interaction between an external charger andan inductive charging coil within IMD 16. In other examples, an externalinductive power supply may transcutaneously power IMD 16 wheneverelectrical stimulation is to occur.

FIG. 6 is a block diagram illustrating an example configuration of anexternal device 70. While external device 70 may generally be describedas a hand-held computing device, the external device may be a notebookcomputer, a cell phone, or a workstation, for example. As illustrated inFIG. 6, external device 70 may include processing circuitry 72, memory74, user interface 76, telemetry circuitry 78, and power source 80.

In general, external device 70 comprises any suitable arrangement ofhardware, alone or in combination with software and/or firmware, toperform the techniques attributed to external device 70, and processingcircuitry 72, user interface 76, and telemetry module 78 of externaldevice 70. Examples of processing circuitry 72 may include one or moreprocessors, such as one or more microprocessors, DSPs, ASICs, FPGAs, orany other equivalent integrated or discrete logic circuitry, as well asany combinations of such components. Examples of memory 74 include RAM,ROM, PROM, EPROM, EEPROM, flash memory, a hard disk, a CD-ROM,comprising executable instructions for causing the one or moreprocessors to perform the actions attributed to them. Moreover, althoughprocessing circuitry 72 and telemetry circuitry 78 are described asseparate circuitry, in some examples, processing circuitry 72 andtelemetry circuitry 78 are functionally integrated. In some examples,processing circuitry 72 and telemetry circuitry 78 correspond toindividual hardware units, such as ASICs, DSPs, FPGAs, or other hardwareunits.

In some examples, memory 74 may further include program information,e.g., stimulation programs, defining the electrical stimulation, similarto those stored in memory 60 of IMD 16. The stimulation programs storedin memory 74 may be downloaded into memory 60 of IMD 16.

User interface 76 may include a button or keypad, lights, a speaker forvoice commands, a display, such as a liquid crystal (LCD),light-emitting diode (LED), or cathode ray tube (CRT). In some examplesthe display may be a touch screen. As discussed in this disclosure,processing circuitry 72 may present and receive information relating toelectrical stimulation and resulting therapeutic effects via userinterface 76. For example, processing circuitry 72 may receive patientinput via user interface 76. The input may be, for example, in the formof pressing a button on a keypad or selecting an icon from a touchscreen.

Processing circuitry 72 may also present information to the patient inthe form of alerts related to delivery of the electrical stimulation topatient 14 or a caregiver via user interface 76. Although not shown,external device 70 may additionally or alternatively include a data ornetwork interface to another computing device, to facilitatecommunication with the other device, and presentation of informationrelating to the electrical stimulation and therapeutic effects aftertermination of the electrical stimulation via the other device.

Telemetry circuitry 78 supports wireless communication between IMD 16and external device 70 under the control of processing circuitry 72.Telemetry circuitry 78 may also be configured to communicate withanother computing device via wireless communication techniques, ordirect communication through a wired connection. In some examples,telemetry circuitry 78 may be substantially similar to telemetrycircuitry 61 of IMD 16 described above, providing wireless communicationvia an RF or proximal inductive medium. In some examples, telemetrycircuitry 61 may include an antenna, which may take on a variety offorms, such as an internal or external antenna.

Examples of local wireless communication techniques employed tofacilitate communication between programmer 70 and another computingdevice include RF communication according to the 802.11 or Bluetoothspecification sets, infrared communication, e.g., according to the IrDAstandard, or other standard or proprietary telemetry protocols. In thismanner, other external devices may be capable of communicating withexternal device 70 without needing to establish a secure wirelessconnection. Power source 80 delivers operating power to the componentsof external device 70. Power source 80 may include a battery and a powergeneration circuit to produce the operating power. In some examples, thebattery may be rechargeable to allow extended operation.

It should be noted system 10, and the techniques described herein, maynot be limited to treatment or monitoring of a human patient. Inalternative examples, system 10 may be implemented in non-humanpatients, e.g., primates, canines, equines, pigs, and felines. Theseother animals may undergo clinical or research therapies benefiting fromthe subject matter of this disclosure. Various examples are describedherein, such as the following examples.

In an example of techniques disclosed, a system 10 may have a first lead21, which may have a first plurality of electrodes 30. System 10 mayhave a second lead 20, which may have a second plurality of electrodes130, 130A. Therapy delivery circuitry 58 may be coupled to the first andsecond leads 21, 20. Therapy delivery circuitry 58 may deliver a firstelectrical stimulation via the first lead 21. The first electricalstimulation may treat obstructive sleep apnea. A second electricalstimulation via the second lead 20 may treat central sleep apnea.Sensing circuitry 56 may sense one or more signals, where each of theone or more signals include respirations. Processing circuitry 57 maydetect apneas based on timing of the respirations. Processing circuitry57 may characterize the apneas as one of obstructive sleep apnea,central sleep apnea, or mixed sleep apnea based on at least one of afrequency spectrum or a morphology of the respirations. In someexamples, processing circuitry 57 may also be configured to provide a“normal/healthy” characterization based on at least one of a frequencyspectrum or a morphology of the respirations, and/or determine that nocharacterization can be made with sufficient confidence, e.g., an“unknown” characterization. Based on the characterization, processingcircuitry 57 may control the therapy delivery circuitry 58 to deliverone of the first electrical stimulation, the second electricalstimulation, both the first and second electrical stimulation incombination, or no stimulation.

FIG. 7 is a flow diagram of an example method 700, e.g., including anauto-sensing feedback loop, for detecting and treating OSA, CSA andcombination OSA/CSA. Method 700 may be a program stored in memory 60 andmay be a therapy program stored within therapy programs 63. Processingcircuitry 57 may execute method 700.

Although described in the context of an example in which IMD 16 performsthe example method 700 of FIG. 7, in other examples, external device 70may perform at least some of the example method of FIG. 7. In someexamples, external device 70 may receive one or more physiologicalsignals or parameters derived from such signals, e.g., from IMD 16 orone or more other implanted or external devices, and determine whetherto deliver one or more electrical stimulation therapies according to theexample of FIG. 7.

In an example, processing circuitry 57 may receive one or morephysiological signals, e.g., sensed by sensing circuitry 56 (702). Eachof the one or more physiological signals may include respirations ofpatient 14. Processing circuitry 57 may detect apnea events based on aprimary biomarker in the one or more physiological signals (704). Aprimary biomarker may be any physiological signal indicating an apneaevent. The physiological signal may come from accelerator 84, ECG sensor82 and/or bio-impedance sensor 86. In some examples, processingcircuitry 57 may detect respirations in such signals based on anamplitude of the signals, an amplitude of a derivative of the signals,and/or an area under the curve of the signals satisfying one or morethresholds, which may be fixed or variable over time. In some examples,the primary biomarker for apnea detection is respiration, and processingcircuitry 57 may detect apnea based on an absence of respiration for athreshold period of time and/or based on morphological feature of therespiration signals.

If no apnea is detected (NO branch of 704), no therapy stimulation isnecessary (706), therapy delivery circuitry 58 remains in an “OFF”condition or powered down, thus conserving power source 62.

If an apnea event is detected (YES branch of 704), processing circuitry57 characterizes each of the apnea events as one of an OSA event, a CSAevent, or a combination OSA/CSA event based on a secondary biomarker(discussed in greater detail below) in the one or more physiologicalsignals (708). Therapy delivery circuitry 58 may provide a firstelectrical stimulation configured to treat OSA in response to a firstone or more of the apnea events being characterized as OSA events (OSAbranch of 708) (710). Therapy delivery circuitry 58 may provide a secondelectrical stimulation configured to treat CSA in response to a secondone or more of apnea events being characterized as CSA events (CSAbranch of 708) (712). Therapy delivery circuitry 58 may provide a thirdelectrical stimulation configured to treat combination OSA/CSA inresponse to a third one or more of the apnea events being characterizedas combination OSA/CSA events (MIXED branch of 708) (714). After eachtherapy administered, processing circuitry 57, continues to receive oneor more physiological signals to detect an apnea event (702).

One of the one or more physiological signals may be an accelerometersignal, a cardiac electrogram signal and/or a bioimpedance signal.Processing circuitry 57 may detect a primary biomarker indicating anOSA, CSA or a combination OSA/CSA event (704). Respiration may be usedas the primary biomarker, and may be discriminated with any combinationof accelerometer 84, ECG sensor 82, or bio-impedance sensor 86. Examplemethod 700 may have greater sensitivity and specificity, the moresensors which are integrated into a respiration sensing algorithm. Asdiscussed above, IMD 16 provides accelerometer 84, ECG sensor 82, orbio-impedance sensor 86 which may be used to quantitatively andqualitatively measure the patient's respiration.

In some examples, 3-axis accelerometer sensor 84 may be used forrespiration detection. While 3-axis accelerometers may be very accurate,they may draw relatively high current and, consequently, may necessitateinfrequent sampling. Thus, 3-axis accelerometer 84 may not be reliedupon continuously, in some examples.

ECG sensing circuitry 82 may also be used for respiration detection. AnECG vector may be taken from CSA lead tip 130A to IMD housing 15, whichmay be used as an electrode. Another subcutaneous ECG vector may betaken from two embedded ECG electrodes located on IMD housing 15,discussed above. ECG sensing is a low-current draw and allows forfrequent sampling. However, ECG sensing is also susceptible to noisefrom within the body (e.g., heart beating, brain activity, etc.).

Bio-impedance sensor 86 may also be used for respiration detection. Avector from CSA lead tip 130A to IMD housing 15 may be useful fordetecting respiration based on bio-impedance. Bio-impedance sensing is amoderate-current draw, which allows for sampling frequency less than ECGsensor 82 but more than accelerometer sensor 84. Bio-impedance fidelityincreases with vector distance, hence CSA lead tip 130A to IMD housing15 may have more signal fidelity than two embedded ECG electrodeslocated on IMD 16.

The primary biomarker may be an ECG derived respiration, an impedancederived respiration, or an accelerometer derived respiration, or arespiration derived from any combination of these signals. Anyone of theprimary biomarkers may provide enough information to detect an apneaevent (704).

In the example method of FIG. 7, processing circuitry 57 detects one ormore apnea events, and responsively characterizes the respiration as oneof OSA, CSA, or mixed OSA/CSA. In other examples, there may be more ofless classifications or characterizations that can be made by processingcircuitry 57.

In some examples, processing circuitry 57 may additionally oralternatively be configured to classify or characterize respiration as“healthy/normal,” e.g., in response to detecting one or more apneaevents. Healthy/normal respiration may be used as a “safety” comparisonwhen determining OSA, CSA, or MIXED apnea event, e.g., to avoid deliveryof stimulation where apneas were misidentified using the primarybiomarker or were correctly identified but were of a transient nature.Processing circuitry 57 may determine that respiration should beclassified as healthy/normal based on the secondary biomarker asdescribed herein, e.g., based on one or both of a frequency ormorphology of one or more respiration signals. Healthy/normalrespiration may be determined as another type of respiration (708). Inresponse to classifying the respiration as healthy/normal, processingcircuitry 57 may control therapy delivery circuitry 58 to suspend orstop delivery of a therapy, e.g., a therapy configured to treat one orboth of OSA and CSA.

In some examples, processing circuitry 57 may additionally be configuredto determine that respiration cannot be classified (708) in response todetecting one or more apneas (704), e.g., because none of the criteriaassociated with other classifications, such as OSA, CSA, mixed OSA/CSA,and/or healthy/normal, are satisfied by the one or more physiologicalsignals indicative of respiration. In response to being unable todetermine one of the classifications, processing circuitry 57 maycontrol therapy delivery circuitry 58 to deliver a default or “safetymode” therapy. The default or safety mode therapy could be selectable bya user and/or could default to the therapy configured to treat mixedOSA/CSA.

In some examples, the classification of a type of respiration based on asecondary biomarker, e.g., 708 of FIG. 7, may include a series ofsequential determinations of whether the respiration signal(s) satisfycriteria for different classifications. For example, if processingcircuitry 57 determines that OSA detected (708), processing circuitry 57may control therapy delivery circuitry 58 deliver OSA therapy (710). IfOSA is not detected (708), processing circuitry 57 may determine whetherCSA is detected (708). If CSA is detected, processing circuitry 57 maycontrol therapy delivery circuitry 58 to deliver therapy configured totreat CSA (712). If CSA is not detected, processing circuitry 57 maydetermine whether one or more criteria to classify respiration as mixedOSA/CSA are satisfied (708) and, if so, deliver both OSA+CSA therapy(714).

If the criteria for mixed OSA/CSA are not satisfied, processingcircuitry 57 may determine whether one or more criteria for“healthy/normal” respiration are satisfied. If the criteria forhealthy/normal respiration are satisfied, processing circuitry 57 maycontrol therapy delivery circuitry 58 to turn therapy off (706). In someexamples, e.g., if processing circuitry 57 is unable to determine any ofthe classifications, IMD 16 may default to a “safety mode” therapydelivery (e.g., could be selectable, but default to mixed therapydelivery). In examples of the present disclosure, if “healthy/normal”detection inconclusive, processing circuitry 57 may default to a “safetymode” therapy delivery (e.g., where mixed therapy delivery may be usedas default; or a programmable selection for OSA therapy, CSA therapy, orMIXED therapy or a no therapy over-ride).

FIGS. 8A, 8B, 8C and 8D are a graphical diagram of a sleep spectrogramaccording to one or more examples. OSA and CSA have differentphysiologic origins, which may be better detected through the creationof a “sleep spectrogram” by morphing several different physiologicalsignals together by processing circuitry 57. In OSA, the upper airwaybecomes partially or completely blocked while patient 14 sleeps. In CSA,there is cessation of respiratory drive resulting in a lack ofrespiratory movements (e.g., a lack of lower brain stem signal). Inmixed OSA/CSA there is a parallel blending of the primary biomarkers.

Processing circuitry 57 may combine the three primary respiration sensorsignals to create a “sleep spectrogram,” which may provide increasedsensitivity and specificity to discriminate between OSA, CSA, or mixedOSA/CSA manifestations and allow automatic and appropriate therapydelivery.

Sleep spectrogram 1000 shows a “healthy/normal” sleep spectrogram, forwhich no therapy may be needed and patient 14 may be sleeping well. Inexamples of the present disclosure, “healthy/normal” respiration may beused as a “safety” comparison or reference point when determining OSA,CSA or mixed OSA/CSA apnea event. Processing circuitry 57 may use sleepspectrogram 1000 or similar respiration signal data to determine a typeof therapy. If processing circuitry 57 determines a “healthy/normal”sleep spectrogram, therapy delivery circuitry 58 remains off. Fromcardiopulmonary sleep spectrogram 1000, “healthy/normal” spectrogramenergy is primarily 0.2 to 0.3 Hz with a predominant “spiked”morphology.

If sleep spectrogram or similar data has features similar to those ofsleep spectrogram 1002, processing circuitry 57 may determine an OSAevent is occurring within patient 14. From cardiopulmonary sleepspectrogram 1002, OSA spectrogram energy is primarily 0.0 to 0.1 Hz witha predominant “spiked” morphology. In response to determining that asleep spectrogram has features like sleep spectrogram 1002, processingcircuitry 57 may then provide a stimulation therapy from therapydelivery circuitry 58 to musculature of a tongue of a patient andproximate to a hypoglossal nerve or both motor points 54A and 54B and/ormotor points 55A and 55B for the OSA detected event (710).

If the sleep spectrogram or similar data has features similar to sleepspectrogram 1004, processing circuitry 57 may determine that a CSA eventis occurring (708). From cardiopulmonary sleep spectrogram 1004, CSAspectrogram energy is primarily 0.0 to 0.1 Hz with a predominant“plateau” or “clipped” morphology. Processing circuitry 57 may thenprovide stimulation therapy from the therapy delivery circuitry 58intravascularly proximate to a phrenic nerve for the CSA detected event(712).

If the sleep spectrogram or similar data has features similar to sleepspectrogram 1006, processing circuitry 57 may determine a mixed OSA/CSAevent in occurring (708). From cardiopulmonary sleep spectrogram 1006,mixed spectrogram energy is primarily 0.0 to 0.1 Hz with a combinationof spikes and plateaus co-relatable to the number of OSA events (spikes)or CSA events (plateaus). Processing circuitry 57 may then providestimulation therapy from the therapy delivery circuitry 58 to themusculature of the tongue of the patient proximate to the hypoglossalnerve or both motor points 54A and 54B and/or motor points 55A and 55Band intravascularly proximate to the phrenic nerve for the combinationOSA/CSA event (714).

Processing circuitry 57 may determine whether one or more criteria foreach of a plurality of classifications is satisfied by a sleepspectrogram or other arrangement of time series of data from one or morerespiration signals. The features of the data compared to the criteriamay be considered secondary biomarkers, and may include frequency and/ormorphology features. In some examples, a criterion for classifying thedata is a frequency criterion, where energy of the signal(s) in one ormore spectra may be compared to each other or one or more thresholds. Insome examples, a criterion for classifying the data is a morphologycriterion, where morphology of the signal(s) may be compared to one ormore criterion. Morphological criteria may include whether the signalsare spiked or plateaued as described above. Morphological criteria mayinclude comparing the signal data to one or more templates, or waveletor other decompositions of the signal to one or more templatedecompositions or thresholds

The techniques of this disclosure may be implemented in a wide varietyof computing devices, medical devices, or any combination thereof. Anyof the described units, modules or components may be implementedtogether or separately as discrete but interoperable logic devices.Depiction of different features as modules or units is intended tohighlight different functional aspects and does not necessarily implythat such modules or units must be realized by separate hardware orsoftware components. Rather, functionality associated with one or moremodules or units may be performed by separate hardware or softwarecomponents or integrated within common or separate hardware or softwarecomponents.

The disclosure contemplates computer-readable storage media comprisinginstructions to cause a processor to perform any of the functions andtechniques described herein. The computer-readable storage media maytake the example form of any volatile, non-volatile, magnetic, optical,or electrical media, such as a RAM, ROM, NVRAM, EEPROM, or flash memorythat is tangible. The computer-readable storage media may be referred toas non-transitory. A server, client computing device, or any othercomputing device may also contain a more portable removable memory typeto enable easy data transfer or offline data analysis.

The techniques described in this disclosure, including those attributedto various modules and various constituent components, may beimplemented, at least in part, in hardware, software, firmware or anycombination thereof. For example, various aspects of the techniques maybe implemented within one or more processors, including one or moremicroprocessors, DSPs, ASICs, FPGAs, or any other equivalent integrated,discrete logic circuitry, or other processing circuitry, as well as anycombinations of such components, remote servers, remote client devices,or other devices. The term “processor” or “processing circuitry” mayrefer to any of the foregoing logic circuitry, alone or in combinationwith other logic circuitry, or any other equivalent circuitry.

Such hardware, software, firmware may be implemented within the samedevice or within separate devices to support the various operations andfunctions described in this disclosure. In addition, any of thedescribed units, modules or components may be implemented together orseparately as discrete but interoperable logic devices. Depiction ofdifferent features as modules or units is intended to highlightdifferent functional aspects and does not necessarily imply that suchmodules or units must be realized by separate hardware or softwarecomponents. Rather, functionality associated with one or more modules orunits may be performed by separate hardware or software components orintegrated within common or separate hardware or software components.For example, any module described herein may include electricalcircuitry configured to perform the features attributed to thatparticular module, such as fixed function processing circuitry,programmable processing circuitry, or combinations thereof.

The techniques described in this disclosure may also be embodied orencoded in an article of manufacture including a computer-readablestorage medium encoded with instructions. Instructions embedded orencoded in an article of manufacture including a computer-readablestorage medium encoded, may cause one or more programmable processors,or other processors, to implement one or more of the techniquesdescribed herein, such as when instructions included or encoded in thecomputer-readable storage medium are executed by the one or moreprocessors. Example computer-readable storage media may include randomaccess memory (RAM), read only memory (ROM), programmable read onlymemory (PROM), erasable programmable read only memory (EPROM),electronically erasable programmable read only memory (EEPROM), flashmemory, a hard disk, a compact disc ROM (CD-ROM), a floppy disk, acassette, magnetic media, optical media, or any other computer readablestorage devices or tangible computer readable media. Thecomputer-readable storage medium may also be referred to as storagedevices.

In some examples, a computer-readable storage medium comprisesnon-transitory medium. The term “non-transitory” may indicate that thestorage medium is not embodied in a carrier wave or a propagated signal.In certain examples, a non-transitory storage medium may store data thatmay, over time, change (e.g., in RAM or cache).

The following examples are illustrative of the techniques describedherein.

Example 1. A method comprising: receiving one or more physiologicalsignals, each of the one or more physiological signals includingrespirations of a patient; detecting apnea events based on a primarybiomarker in the one or more physiological signals; characterizing eachof the apnea events as one of a normal event, OSA (obstructive sleepapnea) event, a CSA (central sleep apnea) event, or a combinationOSA/CSA event based on a secondary biomarker in the one or morephysiological signals; providing a first electrical stimulationconfigured to treat OSA in response to a first one or more of the apneaevents being characterized as OSA events; providing a second electricalstimulation configured to treat CSA in response to a second one or moreof apnea events being characterized as CSA events; and providing a thirdelectrical stimulation configured to treat combination OSA/CSA inresponse to a third one or more of the apnea events being characterizedas combination OSA/CSA events.

Example 2. The method of claim 1, further comprising providing one ofthe first, the second or the third electrical stimulation as a defaultbased on determining that the apnea events cannot be characterized as anormal event, an OSA event, CSA or combination OSA/CSA.

Example 3. The method of example 1, wherein one of the one or morephysiological signals comprise an accelerometer signal.

Example 4. The method of example 1 or 3, wherein one of the one or morephysiological signals comprise a cardiac electrical signal.

Example 5. The method of any of examples 1-4, wherein one of the one ormore physiological signals comprise a bioimpedance signal.

Example 6. The method of any of examples 1-5, wherein the secondarybiomarker comprises at least one of a frequency spectrum or a morphologyof the one or more physiological signals.

Example 7. The method of any of examples 1, 5, or 6, wherein the one ormore physiological signals comprise an accelerometer signal, a cardiacelectrical signal, and a bioimpedance signal.

Example 8. The method of any of examples 1-7, wherein providing thefirst electrical stimulation configured to treat OSA comprisesdelivering the first electrical stimulation via a first lead implantedwithin musculature of a tongue of the patient, and providing the secondelectrical stimulation configured to treat CSA comprises delivering thesecond electrical stimulation via a second lead implantedintravascularly proximate to a phrenic nerve within the patient.

Example 9. The method of any of examples 1-8, wherein providing thethird electrical stimulation comprises providing both the firstelectrical stimulation and the second electrical stimulation.

Example 10. The method of any of examples 1-9, wherein providing thefirst, second, and third electrical stimulations comprises deliveringthe first, second, and third electrical stimulations from a singleimplantable medical device.

Example 11. A system comprising therapy delivery circuitry configured tobe coupled to a first lead comprising a first plurality of electrodesand a second lead comprising a second plurality of electrodes. Thetherapy circuitry is configured to: deliver a first electricalstimulation via the first lead, the first electrical stimulationconfigured to treat obstructive sleep apnea (OSA); and deliver a secondelectrical stimulation via the second lead, the second electricalstimulation configured to treat central sleep apnea (CSA). The systemfurther comprises sensing circuitry configured to sense one or morephysiological signals, each of the one or more physiological signalsincluding respirations of a patient, and processing circuitry. Theprocessing circuitry is configured to: detect apnea events based ontiming of the respirations; determine at least one of a frequencyspectrum or a morphology of the respirations based on the detection ofthe apnea events; characterize the apnea events as one of normal, OSA,CSA, or combination OSA/CSA events based on the at least one of thefrequency spectrum or the morphology of the respirations; and based onthe characterization of the apneas, control the therapy deliverycircuitry to deliver one of no electrical stimulation, the firstelectrical stimulation, the second electrical stimulation, or both thefirst and second electrical stimulation in combination.

Example 12. The system of example 11, wherein the first lead isconfigured to be implanted within musculature of a tongue of a patient.

Example 13. The system of example 11 or 12, wherein the second lead isconfigured to be implanted intravascularly proximate to a phrenic nervewithin the patient.

Example 14. The system of any of examples 11-13, wherein the sensingcircuitry comprises an accelerometer and one of the one or morephysiological signals comprise a motion signal that includes therespirations.

Example 15. The system of any of examples 11-14, wherein the one or morephysiological signals comprise a cardiac electrical signal that includesthe respirations.

Example 16. The system of any of examples 11-15, wherein the one or morephysiological signals comprise a bioimpedance signal that includes therespirations.

Example 17. The system of any of examples 11-16, wherein the processingcircuitry is configured to control the therapy delivery circuitry to bein an off state prior to the detection of the apneas.

Example 18. The system of examples 11-13, wherein the second lead isconfigured to be implanted percutaneously in tissue near the phrenicnerve.

Example 19. An implantable medical device configured to be coupled to afirst lead comprising a first plurality of electrodes and a second leadcomprising a second plurality of electrodes, the implantable medicaldevice comprising therapy delivery circuitry configured to: deliver afirst electrical stimulation via the first lead, the first electricalstimulation configured to treat obstructive sleep apnea (OSA); anddeliver a second electrical stimulation via the second lead, the secondelectrical stimulation configured to treat central sleep apnea (CSA).The implantable medical device further comprises sensing circuitryconfigured sense one or more physiological signals, each of the one ormore physiological signals including respirations of a patient, andprocessing circuitry. The processing circuitry is configured to: detectrespirations in the one or more physiological signals; detect an apneaevent based on the respirations detected in the one or more sensedphysiological signals; characterize the apnea as one of obstructivesleep apnea (OSA), central sleep apnea (CSA), or mixed sleep apnea(OSA/CSA) based on at least one of a frequency spectrum or a morphologyof the respirations; and based on the characterization of the apneas,control the therapy delivery circuitry to deliver one of the firstelectrical stimulation, the second electrical stimulation, or both thefirst and second electrical stimulation in combination.

Example 20. The implantable medical device of example 19, wherein thefirst plurality of electrodes is located along a distal portion of thefirst lead configured to be implanted within musculature of a tongue ofa patient.

Example 21. The implantable medical device of example 19 or 20, whereinthe second plurality of electrodes is located along a distal portion ofthe second lead configured to be implanted intravascularly proximate toa phrenic nerve within the patient.

Example 22. The implantable medical device of any of examples 19-21,wherein the sensing circuitry comprises an accelerometer and one of theone or more physiological signals comprise a motion signal.

Example 23. The implantable medical device of any of examples 19-22,wherein the one or more physiological signals comprise a cardiacelectrical signal.

Example 24. The implantable medical device of any of examples 19-23,wherein the one or more physiological signals comprise a bioimpedancesignal.

Example 25. The implantable medical device of any of examples 19-24,wherein the processing circuitry is configured to turn off the therapydelivery circuitry when the processing circuitry does not detect anapnea event.

Various examples have been described herein. Any combination of thedescribed operations or functions is contemplated. These and otherexamples are within the scope of the following claims.

What is claimed is:
 1. A method comprising: receiving one or morephysiological signals, each of the one or more physiological signalsincluding respirations of a patient; detecting apnea events based on aprimary biomarker in the one or more physiological signals;characterizing each of the apnea events as one of a normal event, OSA(obstructive sleep apnea) event, a CSA (central sleep apnea) event, or acombination OSA/CSA event based on a secondary biomarker in the one ormore physiological signals; providing a first electrical stimulationconfigured to treat OSA in response to a first one or more of the apneaevents being characterized as OSA events; providing a second electricalstimulation configured to treat CSA in response to a second one or moreof apnea events being characterized as CSA events; and providing a thirdelectrical stimulation configured to treat combination OSA/CSA inresponse to a third one or more of the apnea events being characterizedas combination OSA/CSA events.
 2. The method of claim 1, furthercomprising providing one of the first, the second or the thirdelectrical stimulation as a default based on determining that the apneaevents cannot be characterized as a normal event, an OSA event, a CSAevent, or combination OSA/CSA events.
 3. The method of claim 1, whereinone of the one or more physiological signals comprise an accelerometersignal.
 4. The method of claim 1, wherein one of the one or morephysiological signals comprise a cardiac electrical signal.
 5. Themethod of claim 1, wherein one of the one or more physiological signalscomprise a bioimpedance signal.
 6. The method of claim 1, wherein thesecondary biomarker comprises at least one of a frequency spectrum or amorphology of the one or more physiological signals.
 7. The method ofclaim 1, wherein the one or more physiological signals comprise anaccelerometer signal, a cardiac electrical signal, and a bioimpedancesignal.
 8. The method of claim 1, wherein providing the first electricalstimulation configured to treat OSA comprises delivering the firstelectrical stimulation via a first lead implanted within musculature ofa tongue of the patient, and providing the second electrical stimulationconfigured to treat CSA comprises delivering the second electricalstimulation via a second lead implanted intravascularly proximate to aphrenic nerve within the patient.
 9. The method of claim 1, whereinproviding the third electrical stimulation comprises providing both thefirst electrical stimulation and the second electrical stimulation. 10.The method of claim 1, wherein providing the first, second, and thirdelectrical stimulations comprises delivering the first, second, andthird electrical stimulations from a single implantable medical device.11. A system comprising: therapy delivery circuitry configured to becoupled to a first lead comprising a first plurality of electrodes and asecond lead comprising a second plurality of electrodes and configuredto: deliver a first electrical stimulation via the first lead, the firstelectrical stimulation configured to treat obstructive sleep apnea(OSA); and deliver a second electrical stimulation via the second lead,the second electrical stimulation configured to treat central sleepapnea (CSA); sensing circuitry configured to sense one or morephysiological signals, each of the one or more physiological signalsincluding respirations of a patient; and processing circuitry configuredto: detect apnea events based on timing of the respirations; determineat least one of a frequency spectrum or a morphology of the respirationsbased on the detection of the apnea events; characterize the apneaevents as one of normal, OSA, CSA, or combination OSA/CSA events basedon the at least one of the frequency spectrum or the morphology of therespirations; based on the characterization of the apneas, control thetherapy delivery circuitry to deliver one of no electrical stimulation,the first electrical stimulation, the second electrical stimulation, orboth the first and second electrical stimulation in combination.
 12. Thesystem of claim 11, wherein the first lead is configured to be implantedwithin musculature of a tongue of a patient.
 13. The system of claim 11,wherein the second lead is configured to be implanted intravascularlyproximate to a phrenic nerve within the patient.
 14. The system of claim11, wherein the sensing circuitry comprises an accelerometer and one ofthe one or more physiological signals comprise a motion signal thatincludes the respirations.
 15. The system of claim 11, wherein the oneor more physiological signals comprise a cardiac electrical signal thatincludes the respirations.
 16. The system of claim 11, wherein the oneor more physiological signals comprise a bioimpedance signal thatincludes the respirations.
 17. The system of claim 11, wherein theprocessing circuitry is configured to control the therapy deliverycircuitry to be in an off state prior to the detection of the apneas.18. The system of claim 11, wherein the second lead is configured to beimplanted percutaneously in tissue near the phrenic nerve.
 19. Animplantable medical device configured to be coupled to a first leadcomprising a first plurality of electrodes and a second lead comprisinga second plurality of electrodes, the implantable medical devicecomprising: therapy delivery circuitry configured to: deliver a firstelectrical stimulation via the first lead, the first electricalstimulation configured to treat obstructive sleep apnea (OSA); anddeliver a second electrical stimulation via the second lead, the secondelectrical stimulation configured to treat central sleep apnea (CSA);sensing circuitry configured sense one or more physiological signals,each of the one or more physiological signals including respirations ofa patient; and processing circuitry configured to: detect respirationsin the one or more physiological signals; detect an apnea event based onthe respirations detected in the one or more physiological signals;characterize the apnea as one of obstructive sleep apnea (OSA), centralsleep apnea (CSA), or mixed sleep apnea (OSA/CSA) based on at least oneof a frequency spectrum or a morphology of the respirations; based onthe characterization of the apneas, control the therapy deliverycircuitry to deliver one of the first electrical stimulation, the secondelectrical stimulation, or both the first and second electricalstimulation in combination.
 20. The implantable medical device of claim19, wherein the first plurality of electrodes is located along a distalportion of the first lead configured to be implanted within musculatureof a tongue of a patient.
 21. The implantable medical device of claim19, wherein the second plurality of electrodes is located along a distalportion of the second lead configured to be implanted intravascularlyproximate to a phrenic nerve within the patient.
 22. The implantablemedical device of claim 19, wherein the sensing circuitry comprises anaccelerometer and one of the one or more physiological signals comprisea motion signal.
 23. The implantable medical device of claim 19, whereinthe one or more physiological signals comprise a cardiac electricalsignal.
 24. The implantable medical device of claim 19, wherein the oneor more physiological signals comprise a bioimpedance signal.
 25. Theimplantable medical device of claim 19, wherein the processing circuitryis configured to turn off the therapy delivery circuitry when theprocessing circuitry does not detect an apnea event.